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Research ArticleOriginal Article
Open Access

Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness

Suliman A. Alsagaby
Saudi Medical Journal April 2019, 40 (4) 328-338; DOI: https://doi.org/10.15537/smj.2019.4.23380
Suliman A. Alsagaby
From the Department of Medical Laboratories Sciences, College of Applied Medical Sciences, Majmaah University, Majmaah, Kingdom of Saudi Arabia
MSc, PhD
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    Figure 1

    Nine of the chronic lymphocytic leukemia (CLL) -related proteins had transcript expression that predicted time-to-first treatment (TTFT) in CLL patients. The median expression of the transcripts of interest was used to divide CLL patients into 2 groups: low-expression group, in which the expression of a transcript of interest was smaller than its median, and high-expression group, where the expression of a transcript of interest was greater than its median. This step was carried out independently for each transcript of interest. A-J) The TTFT in the low expression and high expression groups was compared using Kaplan-Meier curve. K) Patients with discordant expression of HNRNPA0 and HNRNPD were not included in the analysis.

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    Figure 2

    Seven of the chronic lymphocytic leukemia (CLL)-related proteins processed transcript expression that predicted overall survival (OS) in CLL patients. Chronic lymphocytic leukemia patients were divided into 2 groups based on the median expression of the transcripts of interest; low-expression group (transcript expression <median expression) and high-expression group (transcript expression >median expression). This step was performed independently for each one of the transcripts of interest. A-G) Kaplan-Meier curve was utilized to compare the OS of the low-expression and high-expression groups. H) Patients with discordant expression of HIST1C1H and HNRNPUL2 were not included in the analysis.

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    Figure 3

    Heatmap presentation of the correlation between HNRNPUL2 and genes of interest in chronic lymphocytic leukemia (CLL) patients. The interrogation of Reactome database reported a significant enrichment of the cell cycle pathway by 101 genes of the genes whose expression significantly correlated with the expression of HNRNPUL2 in the CLL transcriptomics data sets (GSE39671; n=130). Excel software was used to sort the 130 CLL patients from left to right based on the ascending expression HNRNPUL2 (from lowest expression to highest expression). Then, the 101 genes were sorted from top to bottom on the bases of their Pearson scores (from 0.74-0.50), with HNRNPUL2 being at the top of the list. A) Heatmapper was used to construct a heatmap graphic based on the expression of the 101 cell cycle gens and HNRNPUL2 in the 130 patients. B) Of the other genes that correlated with the expression of HNRNPUL2, 7 (Pearson score ranged from 0.74-0.50) were previously shown to drive the progression of CLL.

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    Figure 4

    Increased expression of HNRNPUL2 was indicative of poor prognosis of different types of cancer. The prognostic potential of HNRNPUL2 was assessed in independent transcriptomics data sets of various malignancies from TCGA using cBioPortal and OQL. Different z scores of HNRNPUL2 expression were applied on the TCGA transcriptomics data sets to divide patients into 2 groups; low expression group (HNRNPUL2 expression <z score) and high expression group (HNRNPUL2 expression >z score). Increased expression of HNRNPUL2 was found to significantly predict short overall survival (OS) or short relapse free survival (RFS) in 6 independent transcriptomics data sets of different types of cancer. A) Liver hepatocellular carcinoma (TCGA, Provisional) with z score = -0.12. B) Acute myeloid leukemia (TCGA, Provisional) with z score = 0.413. C) Acute myeloid leukemia (TCGA, NEJM 2013) with z score = 0.38. D) Prostate adenocarcinoma (TCGA, Provisional) with z score = 1.4. E) Lung squamous cell carcinoma (TCGA, Provisional) with z score = 1. F) Bladder urothelial carcinoma (TCGA, Provisional) with z score = -0.4. OQL - onco query language, TCGA - The Cancer Genomic Atlas.

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Saudi Medical Journal: 40 (4)
Saudi Medical Journal
Vol. 40, Issue 4
1 Apr 2019
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Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness
Suliman A. Alsagaby
Saudi Medical Journal Apr 2019, 40 (4) 328-338; DOI: 10.15537/smj.2019.4.23380

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Transcriptomics-based validation of the relatedness of heterogeneous nuclear ribonucleoproteins to chronic lymphocytic leukemia as potential biomarkers of the disease aggressiveness
Suliman A. Alsagaby
Saudi Medical Journal Apr 2019, 40 (4) 328-338; DOI: 10.15537/smj.2019.4.23380
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